The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

Galisteo, 2008, Effects of dietary fibers on disturbances clustered in the metabolic syndrome, J. Nutr. Biochem., 19, 71, 10.1016/j.jnutbio.2007.02.009 Venn, 2004, Cereal grains, legumes and diabetes, Eur. J. Clin. Nutr., 58, 1443, 10.1038/sj.ejcn.1601995 Delzenne, 2005, A place for dietary fibre in the management of the metabolic syndrome, Curr. Opin. Clin. Nutr. Metab. Care., 8, 636, 10.1097/01.mco.0000171124.06408.71 Marlett, 2002, Position of the American Dietetic Association: health implications of dietary fiber, J. Am. Diet. Assoc., 102, 993, 10.1016/S0002-8223(02)90228-2 Nicholson, 2012, Host-gut microbiota metabolic interactions, Science., 336, 1262, 10.1126/science.1223813 Roy, 2006, Short-chain fatty acids: ready for prime time?, Nutr. Clin. Pract., 21, 351, 10.1177/0115426506021004351 van Hoek, 2012, Redox balance is key to explaining full vs. partial switching to low-yield metabolism, BMC Syst. Biol., 6, 22, 10.1186/1752-0509-6-22 Cook, 1998, Review article: short chain fatty acids in health and disease, Aliment. Pharmacol. Ther., 12, 499, 10.1046/j.1365-2036.1998.00337.x Hijova, 2007, Short chain fatty acids and colonic health, Bratisl. Lek. Listy., 108, 354 Binder, 2010, Role of colonic short-chain fatty acid transport in diarrhea, Annu. Rev. Physiol., 72, 297, 10.1146/annurev-physiol-021909-135817 Cummings, 1987, Short chain fatty acids in human large intestine, portal, hepatic and venous blood, Gut., 28, 1221, 10.1136/gut.28.10.1221 Topping, 2001, Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides, Physiol. Rev., 81, 1031, 10.1152/physrev.2001.81.3.1031 Ruppin, 1980, Absorption of short-chain fatty acids by the colon, Gastroenterology., 78, 1500, 10.1016/S0016-5085(19)30508-6 Dawson, 1964, Absorption of short chain fatty acids in man, Proc. Soc. Exp. Biol. Med., 117, 97, 10.3181/00379727-117-29505 Rechkemmer, 1988, Fermentation of polysaccharides and absorption of short chain fatty acids in the mammalian hindgut, Comp. Biochem. Physiol. A., 90, 563, 10.1016/0300-9629(88)90668-8 Hu, 2010, Activation of the AMP activated protein kinase by short-chain fatty acids is the main mechanism underlying the beneficial effect of a high fiber diet on the metabolic syndrome, Med. Hypotheses., 74, 123, 10.1016/j.mehy.2009.07.022 Gao, 2009, Butyrate improves insulin sensitivity and increases energy expenditure in mice, Diabetes., 58, 1509, 10.2337/db08-1637 Donohoe, 2011, The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon, Cell Metab., 13, 517, 10.1016/j.cmet.2011.02.018 Blouin, 2011, Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex, Int. J. Cancer., 128, 2591, 10.1002/ijc.25599 Scharlau, 2009, Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre, Mutat. Res., 682, 39, 10.1016/j.mrrev.2009.04.001 Tang, 2011, G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer, Int. J. Cancer., 128, 847, 10.1002/ijc.25638 Hamer, 2008, Review article: the role of butyrate on colonic function, Aliment. Pharmacol. Ther., 27, 104, 10.1111/j.1365-2036.2007.03562.x Harig, 1989, Treatment of diversion colitis with short-chain-fatty acid irrigation, N. Engl. J. Med., 320, 23, 10.1056/NEJM198901053200105 Breuer, 1991, Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report, Dig. Dis. Sci., 36, 185, 10.1007/BF01300754 Vernia, 1995, Short-chain fatty acid topical treatment in distal ulcerative colitis, Aliment. Pharmacol. Ther., 9, 309, 10.1111/j.1365-2036.1995.tb00386.x Scheppach, 1996, Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Study Group, Dig. Dis. Sci., 41, 2254, 10.1007/BF02071409 Di Sabatino, 2005, Oral butyrate for mildly to moderately active Crohn's disease, Aliment. Pharmacol. Ther., 22, 789, 10.1111/j.1365-2036.2005.02639.x Flint, 2008, Polysaccharide utilization by gut bacteria potential for new insights from genomic analysis, Nat. Rev. Microbiol., 6, 121, 10.1038/nrmicro1817 Bingham, 2003, Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study, Lancet., 361, 1496, 10.1016/S0140-6736(03)13174-1 Musso, 2011, Interactions between gut microbiota and host metabolism predisposing to obesity and diabetes, Annu. Rev. Med., 62, 361, 10.1146/annurev-med-012510-175505 Bergman, 1990, Energy contributions of volatile fatty acids from the gastrointestinal tract in various species, Physiol. Rev., 70, 567, 10.1152/physrev.1990.70.2.567 Levrat, 1991, High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin, J. Nutr., 121, 1730, 10.1093/jn/121.11.1730 Hedemann, 2009, The thickness of the intestinal mucous layer in the colon of rats fed various sources of non-digestible carbohydrates, Br. J. Nutr., 102, 117, 10.1017/S0007114508143549 Marsono, 1993, Plasma lipids and large bowel volatile fatty acids in pigs fed on white rice, brown rice and rice bran, Br. J. Nutr., 70, 503, 10.1079/BJN19930144 Bird, 2000, Coarse brown rice increases fecal and large bowel short-chain fatty acids and starch but lowers calcium in the large bowel of pigs, J. Nutr., 130, 1780, 10.1093/jn/130.7.1780 Haenen, 2013, A diet high in resistant starch modulates microbiota composition, SCFA concentrations, and gene expression in pig intestine, J. Nutr., 143, 274, 10.3945/jn.112.169672 Topping, 1993, Dietary fat and fiber alter large bowel and portal venous volatile fatty acids and plasma cholesterol but not biliary steroids in pigs, J. Nutr., 123, 133, 10.1093/jn/123.1.133 Cummings, 1996, Digestion and physiological properties of resistant starch in the human large bowel, Br. J. Nutr., 75, 733, 10.1079/BJN19960177 van Munster, 1994, Effect of resistant starch on colonic fermentation, bile acid metabolism, and mucosal proliferation, Dig. Dis. Sci., 39, 834, 10.1007/BF02087431 Holt, 1996, Effects of acarbose on fecal nutrients, colonic pH, and short-chain fatty acids and rectal proliferative indices, Metabolism., 45, 1179, 10.1016/S0026-0495(96)90020-7 Fleming, 1985, Influence of frequent and long-term bean consumption on colonic function and fermentation, Am. J. Clin. Nutr., 41, 909, 10.1093/ajcn/41.5.909 Jenkins, 1998, Physiological effects of resistant starches on fecal bulk, short chain fatty acids, blood lipids and glycemic index, J. Am. Coll. Nutr., 17, 609, 10.1080/07315724.1998.10718810 Holtug, 1992, An in vitro study of short-chain fatty acid concentrations, production and absorption in pig (Sus scrofa) colon, Comp. Biochem. Physiol. Comp. Physiol., 103, 189, 10.1016/0300-9629(92)90262-O Smiricky-Tjardes, 2003, Dietary galactooligosaccharides affect ileal and total-tract nutrient digestibility, ileal and fecal bacterial concentrations, and ileal fermentative characteristics of growing pigs, J. Anim. Sci., 81, 2535, 10.2527/2003.81102535x Velázquez, 2000, Effect of oligosaccharides and fibre substitutes on short-chain fatty acid production by human faecal microflora, Anaerobe., 6, 87, 10.1006/anae.1999.0318 Bourquin, 1992, Short-chain fatty acid production and fiber degradation by human colonic bacteria: effects of substrate and cell wall fractionation procedures, J. Nutr., 122, 1508, 10.1093/jn/122.7.1508 Bergman, 1965, Interconversions and production of volatile fatty acids in the sheep rumen, Biochem. J., 97, 53, 10.1042/bj0970053 Pouteau, 1998, Production rate of acetate during colonic fermentation of lactulose: a stable-isotope study in humans, Am. J. Clin. Nutr., 68, 1276, 10.1093/ajcn/68.6.1276 Pouteau, 2003, Production rates and metabolism of short-chain fatty acids in the colon and whole body using stable isotopes, Proc. Nutr. Soc., 62, 87, 10.1079/PNS2003208 Thompson, 1990, Sources of propionate in inborn errors of propionate metabolism, Metabolism., 39, 1133, 10.1016/0026-0495(90)90084-P Cherrington, 1991, Short-chain organic acids at ph 5.0 kill Escherichia coli and Salmonella spp. without causing membrane perturbation, J. Appl. Bacteriol., 70, 161, 10.1111/j.1365-2672.1991.tb04442.x Prohászka, 1990, The role of intestinal volatile fatty acids in the Salmonella shedding of pigs, Zentralbl. Veterinarmed. B., 37, 570 Walker, 2005, pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon, Appl. Environ. Microbiol., 71, 3692, 10.1128/AEM.71.7.3692-3700.2005 Duncan, 2009, The role of pH in determining the species composition of the human colonic microbiota, Environ. Microbiol., 11, 2112, 10.1111/j.1462-2920.2009.01931.x Xu, 2003, Honor thy symbionts, Proc. Natl. Acad. Sci. USA., 100, 10452, 10.1073/pnas.1734063100 Zoetendal, 2001, The host genotype affects the bacterial community in the human gastrointestinal tract, Microb. Ecol. Health Dis., 13, 129 Abubucker, 2012, Metabolic reconstruction for metagenomic data and its application to the human microbiome, PLOS Comput. Biol., 8, e1002358, 10.1371/journal.pcbi.1002358 Macfarlane, 2003, Regulation of short-chain fatty acid production, Proc. Nutr. Soc., 62, 67, 10.1079/PNS2002207 Veeneman, 2004, Comparison of amino acid oxidation and urea metabolism in haemodialysis patients during fasting and meal intake, Nephrol. Dial. Transplant., 19, 1533, 10.1093/ndt/gfh236 Millet, 2010, Prediction of in vivo short-chain fatty acid production in hindgut fermenting mammals: problems and pitfalls, Crit. Rev. Food Sci. Nutr., 50, 605, 10.1080/10408390802565939 Miller, 1996, Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora, Appl. Environ. Microbiol., 62, 1589, 10.1128/aem.62.5.1589-1592.1996 Fischbach, 2011, Eating for two: how metabolism establishes interspecies interactions in the gut, Cell Host Microbe., 10, 336, 10.1016/j.chom.2011.10.002 Macy, 1978, Pathway of succinate and propionate formation in Bacteroides fragilis, J. Bacteriol., 134, 84, 10.1128/jb.134.1.84-91.1978 Macy, 1979, The biology of gastrointestinal bacteroides, Annu. Rev. Microbiol., 33, 561, 10.1146/annurev.mi.33.100179.003021 Pryde, 2002, The microbiology of butyrate formation in the human colon, FEMS Microbiol. Lett., 217, 133, 10.1111/j.1574-6968.2002.tb11467.x Ragsdale, 2008, Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation, Biochim. Biophys. Acta., 1784, 1873, 10.1016/j.bbapap.2008.08.012 Duncan, 2004, Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product, Appl. Environ. Microbiol., 70, 5810, 10.1128/AEM.70.10.5810-5817.2004 Louis, 2009, Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine, FEMS Microbiol. Lett., 294, 1, 10.1111/j.1574-6968.2009.01514.x Duncan, 2002, Acetate Utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine, Appl. Environ. Microbiol., 68, 5186, 10.1128/AEM.68.10.5186-5190.2002 Venema, 2010, Role of gut microbiota in the control of energy and carbohydrate metabolism, Curr. Opin. Clin. Nutr. Metab. Care., 13, 432, 10.1097/MCO.0b013e32833a8b60 Duncan, 2004, Contribution of acetate to butyrate formation by human faecal bacteria, Br. J. Nutr., 91, 915, 10.1079/BJN20041150 el-Khoury, 1994, Similar 24-h pattern and rate of carbon dioxide production, by indirect calorimetry vs. stable isotope dilution, in healthy adults under standardized metabolic conditions, J. Nutr., 124, 1615, 10.1093/jn/124.9.1615 Annison, 2003, Acetylated, propionylated or butyrylated starches raise large bowel short-chain fatty acids preferentially when fed to rats, J. Nutr., 133, 3523, 10.1093/jn/133.11.3523 Jacobs, 1986, Relationship between colonic luminal pH, cell proliferation, and colon carcinogenesis in 1,2-dimethylhydrazine treated rats fed high fiber diets, Cancer Res., 46, 1727 Ward, 1987, Gastrointestinal pH measurement in rats: influence of the microbial flora, diet and fasting, Lab. Anim., 21, 216, 10.1258/002367787781268693 Campbell, 1997, Selected indigestible oligosaccharides affect large bowel mass, cecal and fecal short-chain fatty acids, pH and microflora in rats, J. Nutr., 127, 130, 10.1093/jn/127.1.130 Murase, 1995, Determination of portal short-chain fatty acids in rats fed various dietary fibers by capillary gas chromatography, J. Chromatogr. B Biomed. Appl., 664, 415, 10.1016/0378-4347(94)00491-M Fushimi, 2006, Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed a cholesterol-rich diet, Br. J. Nutr., 95, 916, 10.1079/BJN20061740 Demigné, 1995, Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes, Br. J. Nutr., 74, 209, 10.1079/BJN19950124 Todesco, 1991, Propionate lowers blood glucose and alters lipid metabolism in healthy subjects, Am. J. Clin. Nutr., 54, 860, 10.1093/ajcn/54.5.860 Stoddart, 2008, International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions, Pharmacol. Rev., 60, 405, 10.1124/pr.108.00802 Ulven, 2012, Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets, Front. Endocrinol. (Lausanne)., 3, 111, 10.3389/fendo.2012.00111 Tazoe, 2008, Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions, J. Physiol. Pharmacol., 59, 251 Sellin, 1999, SCFAs: the enigma of weak electrolyte transport in the colon, News Physiol. Sci., 14, 58 Vidyasagar, 2005, Role of short-chain fatty acids in colonic HCO(3) secretion, Am. J. Physiol. Gastrointest. Liver Physiol., 288, G1217, 10.1152/ajpgi.00415.2004 Mascolo, 1991, Mechanism of short-chain fatty acid uptake by apical membrane vesicles of rat distal colon, Gastroenterology., 101, 331, 10.1016/0016-5085(91)90008-9 Harig, 1996, Transport of n-butyrate into human colonic luminal membrane vesicles, Am. J. Physiol., 271, G415 Harig, 1991, Transport of propionate by human ileal brush-border membrane vesicles, Am. J. Physiol., 260, G776 Hadjiagapiou, 2000, Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1, Am. J. Physiol. Gastrointest. Liver Physiol., 279, G775, 10.1152/ajpgi.2000.279.4.G775 Teramae, 2010, The cellular expression of SMCT2 and its comparison with other transporters for monocarboxylates in the mouse digestive tract, Biomed. Res., 31, 239, 10.2220/biomedres.31.239 Takebe, 2005, Histochemical demonstration of a Na(+)-coupled transporter for short-chain fatty acids (slc5a8) in the intestine and kidney of the mouse, Biomed. Res., 26, 213, 10.2220/biomedres.26.213 Gupta, 2006, SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter, Life Sci., 78, 2419, 10.1016/j.lfs.2005.10.028 Gonçalves, 2011, Characterization of butyrate uptake by nontransformed intestinal epithelial cell lines, J. Membr. Biol., 240, 35, 10.1007/s00232-011-9340-3 Musch, 2001, SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells, Am. J. Physiol. Gastrointest. Liver Physiol., 280, G687, 10.1152/ajpgi.2001.280.4.G687 Tyagi, 2002, Mechanism of n-butyrate uptake in the human proximal colonic basolateral membranes, Am. J. Physiol. Gastrointest. Liver Physiol., 282, G676, 10.1152/ajpgi.00173.2000 Gill, 2005, Expression and membrane localization of MCT isoforms along the length of the human intestine, Am. J. Physiol. Cell Physiol., 289, C846, 10.1152/ajpcell.00112.2005 Halestrap, 2004, The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond, Pflugers Arch., 447, 619, 10.1007/s00424-003-1067-2 Islam, 2008, Mouse organic anion transporter 2 (mOat2) mediates the transport of short chain fatty acid propionate, J. Pharmacol. Sci., 106, 525, 10.1254/jphs.SC0070291 Shin, 2007, Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate, Hepatology., 45, 1046, 10.1002/hep.21596 Roediger, 1982, Utilization of nutrients by isolated epithelial cells of the rat colon, Gastroenterology., 83, 424, 10.1016/S0016-5085(82)80339-9 Clausen, 1995, Kinetic studies on colonocyte metabolism of short chain fatty acids and glucose in ulcerative colitis, Gut., 37, 684, 10.1136/gut.37.5.684 J⊘rgensen, 1997, Oxidation of short and medium chain C2-C8 fatty acids in Sprague-Dawley rat colonocytes, Gut., 40, 400, 10.1136/gut.40.3.400 Ballard, 1972, Supply and utilization of acetate in mammals, Am. J. Clin. Nutr., 25, 773, 10.1093/ajcn/25.8.773 Knowles, 1974, Production and utilization of acetate in mammals, Biochem. J., 142, 401, 10.1042/bj1420401 Bloemen, 2009, Short chain fatty acids exchange across the gut and liver in humans measured at surgery, Clin. Nutr., 28, 657, 10.1016/j.clnu.2009.05.011 Wiltrout, 1972, Contribution of propionate to glucose synthesis in the lactating and nonlactating cow, J. Dairy Sci., 55, 307, 10.3168/jds.S0022-0302(72)85487-0 Bloemen, 2010, Short chain fatty acids exchange: is the cirrhotic, dysfunctional liver still able to clear them?, Clin. Nutr., 29, 365, 10.1016/j.clnu.2009.10.002 Reilly, 1993, Metabolism and potential clinical applications of short-chain fatty acids, Clin. Nutr., 12, S97, 10.1016/S0261-5614(09)90016-4 Brown, 2003, The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids, J. Biol. Chem., 278, 11312, 10.1074/jbc.M211609200 Le Poul, 2003, Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation, J. Biol. Chem., 278, 25481, 10.1074/jbc.M301403200 Nilsson, 2003, Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids, Biochem. Biophys. Res. Commun., 303, 1047, 10.1016/S0006-291X(03)00488-1 Regard, 2008, Anatomical profiling of G protein-coupled receptor expression, Cell., 135, 561, 10.1016/j.cell.2008.08.040 Hong, 2005, Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43, Endocrinology., 146, 5092, 10.1210/en.2005-0545 Ge, 2008, Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids, Endocrinology., 149, 4519, 10.1210/en.2008-0059 Samuel, 2008, Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41, Proc. Natl. Acad. Sci. USA., 105, 16767, 10.1073/pnas.0808567105 Sleeth, 2010, Free fatty acid receptor 2 and nutrient sensing a proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation, Nutr. Res. Rev., 23, 135, 10.1017/S0954422410000089 Bjursell, 2011, Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet, Am. J. Physiol. Endocrinol. Metab., 300, E211, 10.1152/ajpendo.00229.2010 Zaibi, 2010, Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids, FEBS Lett., 584, 2381, 10.1016/j.febslet.2010.04.027 Xiong, 2004, Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41, Proc. Natl. Acad. Sci. USA., 101, 1045, 10.1073/pnas.2637002100 Covington, 2006, The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing, Biochem. Soc. Trans., 34, 770, 10.1042/BST0340770 Yamashita, 2007, Improvement of obesity and glucose tolerance by acetate in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats, Biosci. Biotechnol. Biochem., 71, 1236, 10.1271/bbb.60668 Lin, 2012, Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms, PLoS ONE., 7, e35240, 10.1371/journal.pone.0035240 Kondo, 2009, Acetic acid upregulates the expression of genes for fatty acid oxidation enzymes in liver to suppress body fat accumulation, J. Agric. Food Chem., 57, 5982, 10.1021/jf900470c Kondo, 2009, Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects, Biosci. Biotechnol. Biochem., 73, 1837, 10.1271/bbb.90231 Zydowo, 1993, Acetate-induced changes of adenine nucleotide levels in rat liver, Metabolism., 42, 644, 10.1016/0026-0495(93)90225-D Lin, 2005, Metabolic control through the PGC-1 family of transcription coactivators, Cell Metab., 1, 361, 10.1016/j.cmet.2005.05.004 Jäger, 2007, AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α, Proc. Natl. Acad. Sci. USA., 104, 12017, 10.1073/pnas.0705070104 Minokoshi, 2002, Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase, Nature., 415, 339, 10.1038/415339a Yu, 2004, Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition, Diabetologia., 47, 2012, 10.1007/s00125-004-1570-9 Robertson, 2005, Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism, Am. J. Clin. Nutr., 82, 559, 10.1093/ajcn/82.3.559 Suokas, 1988, Acute cardiovascular and metabolic effects of acetate in men, Alcohol. Clin. Exp. Res., 12, 52, 10.1111/j.1530-0277.1988.tb00132.x Al-Lahham, 2010, Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms, Biochim. Biophys. Acta., 1801, 1175, 10.1016/j.bbalip.2010.07.007 Carmen, 2006, Signalling mechanisms regulating lipolysis, Cell. Signal., 18, 401, 10.1016/j.cellsig.2005.08.009 Houslay, 1997, Tailoring cAMP-signalling responses through isoform multiplicity, Trends Biochem. Sci., 22, 217, 10.1016/S0968-0004(97)01050-5 Kimura, 2013, The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43, Nat. Commun., 4, 1829, 10.1038/ncomms2852 Friedman, 1998, Leptin and the regulation of body weight in mammals, Nature., 395, 763, 10.1038/27376 Sakakibara, 2006, Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KK-A(y) mice, Biochem. Biophys. Res. Commun., 344, 597, 10.1016/j.bbrc.2006.03.176 Boillot, 1995, Effects of dietary propionate on hepatic glucose production, whole-body glucose utilization, carbohydrate and lipid metabolism in normal rats, Br. J. Nutr., 73, 241, 10.1079/BJN19950026 Batterham, 2002, Gut hormone PYY(3-36) physiologically inhibits food intake, Nature., 418, 650, 10.1038/nature00887 van den Hoek, 2004, PYY3-36 reinforces insulin action on glucose disposal in mice fed a high-fat diet, Diabetes., 53, 1949, 10.2337/diabetes.53.8.1949 Boey, 2006, Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity, Diabetologia., 49, 1360, 10.1007/s00125-006-0237-0 Karaki, 2008, Expression of the short-chain fatty acid receptor, GPR43, in the human colon, J. Mol. Histol., 39, 135, 10.1007/s10735-007-9145-y Karaki, 2006, Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine, Cell Tissue Res., 324, 353, 10.1007/s00441-005-0140-x Tazoe, 2009, Expression of short-chain fatty acid receptor in the human colon, Biomed Res., 30, 149, 10.2220/biomedres.30.149 Tolhurst, 2012, Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein–coupled receptor FFAR2, Diabetes., 61, 364, 10.2337/db11-1019 Cherbut, 1998, Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat, Am. J. Physiol., 275, G1415 Cuche, 2000, Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway, Am. J. Physiol. Gastrointest. Liver Physiol., 279, G925, 10.1152/ajpgi.2000.279.5.G925 Barrera, 2011, GLP-1 and energy balance: an integrated model of short-term and long-term control, Nat. Rev. Endocrinol., 7, 507, 10.1038/nrendo.2011.77 Zhou, 2008, Dietary resistant starch upregulates total GLP-1 and PYY in a sustained day-long manner through fermentation in rodents, Am. J. Physiol. Endocrinol. Metab., 295, E1160, 10.1152/ajpendo.90637.2008 Hooda, 2010, Dietary oat beta-glucan reduces peak net glucose flux and insulin production and modulates plasma incretin in portal-vein catheterized grower pigs, J. Nutr., 140, 1564, 10.3945/jn.110.122721 Freeland, 2010, Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-alpha, Br. J. Nutr., 103, 460, 10.1017/S0007114509991863 Rodwell, 1976, Regulation of HMG-CoA reductase, Adv. Lipid Res., 14, 1, 10.1016/B978-0-12-024914-5.50008-5 Bush, 1971, Study of the mechanism of inhibition of ketogenesis by propionate in bovine liver, Can. J. Anim. Sci., 51, 121, 10.4141/cjas71-016 Wright, 1990, Propionate inhibits hepatocyte lipid synthesis, Proc. Soc. Exp. Biol. Med., 195, 26, 10.3181/00379727-195-43113 Hara, 1999, Short-chain fatty acids suppress cholesterol synthesis in rat liver and intestine, J. Nutr., 129, 942, 10.1093/jn/129.5.942 Carling, 1989, Purification and characterization of the AMP-activated protein kinase, Eur. J. Biochem., 186, 129, 10.1111/j.1432-1033.1989.tb15186.x Corton, 1994, Role of the AMP-activated protein kinase in the cellular stress response, Curr. Biol., 4, 315, 10.1016/S0960-9822(00)00070-1 Henin, 1995, Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP-activated protein kinase, FASEB J., 9, 541, 10.1096/fasebj.9.7.7737463 Turnbaugh, 2006, An obesity-associated gut microbiome with increased capacity for energy harvest, Nature., 444, 1027, 10.1038/nature05414 Murphy, 2010, Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models, Gut., 59, 1635, 10.1136/gut.2010.215665 Schwiertz, 2010, Microbiota and SCFA in lean and overweight healthy subjects, Obesity (Silver Spring)., 18, 190, 10.1038/oby.2009.167 Bäckhed, 2007, Mechanisms underlying the resistance to diet-induced obesity in germ-free mice, Proc. Natl. Acad. Sci. USA., 104, 979, 10.1073/pnas.0605374104 H⊘verstad, 1986, Short-chain fatty acids in germfree mice and rats, J. Nutr., 116, 1772, 10.1093/jn/116.9.1772 Ley, 2005, Obesity alters gut microbial ecology, Proc. Natl. Acad. Sci. USA., 102, 11070, 10.1073/pnas.0504978102 Ley, 2006, Microbial ecology: human gut microbes associated with obesity, Nature., 444, 1022, 10.1038/4441022a Khan, 2002, Effect of substrate concentration on short chain fatty acid production in in vitro cultures of human faeces, Microb Ecol Health Dis., 14, 160